Pharmaceutical, chemical, biological, biochemical or biotech processes are, in increasing measure, performed in single-use containers (also referred to as disposables, or disposable bioreactors) as process containers. Such single-use containers can be, for example, flexible containers, e.g. bags, tubes or fermenters, or bioreactors. Bioreactors or fermenters frequently possess supply, and drain, lines, which can, for example, be embodied as tubes. In the supply, and drain, lines, also rigid tubular pieces can be inserted. After terminating a process, single-use containers can be disposed of. In this way, complex cleaning—and sterilization methods are avoided. Especially, through the use of single-use containers, the risk of cross contamination is prevented and, therewith, process safety is increased.
The processes performed in single-use containers proceed in a closed system, i.e. without connection to the environment outside the single-use containers. Since, frequently, sterile conditions are required, single-use container must be sterilized before introducing the process media. Frequently used for this purpose in biochemical, biological, biotechnological and pharmaceutical applications is gamma radiation. Also, in processes proceeding in a single-use fermenter or single-use reactor, the penetration of impurities, especially germs, from the environment into the interior of the process container must be prevented, in order not to degrade or corrupt the process flow.
In order to monitor or check the processes, it can be necessary to measure physical or chemical, measured variables of the media contained in the process container. Measured variables to be monitored can be, for example, temperature, pH-value, cell density, optical transmission or a concentration of a chemical substance, for example, a certain kind of ion, a certain element or a certain compound.
In published international patent application WO 2009/071829 A2 and German Offenlegungsschrift DE 10 2006 005 533 A1, complex mechanical coupling systems are described, which enable sterile introduction of an externally sterilized sensor into a single-use container.
Known from German Gebrauchsmuster DE 20 2007 000 152 U1 is an apparatus for securing an optical probe on a container having a flexible wall. In this case, the probe lies with a rear surface portion against an inner side of the container wall and extends with a central piece through an opening in the container wall, wherein the central piece is affixed by clamping to the container wall.
In order to configure the use of a container serving as a single-use fermenter or a single-use bioreactor especially simply, the potentiometric probe can be installed, already before the sterilization (to be effected, for example, by irradiation with gamma radiation), fixedly in a wall of the container and remain there for the duration of storage and use. While the actual use time of single-use containers amounts to only a few weeks, storage times can occur in the order of magnitude of one or more years.
Potentiometric sensors, for example, pH-glass electrodes or ion-selective electrodes, which are frequently embodied as single-rod, measuring chains, have a reference half cell and a measuring half cell, which contain a liquid or gel-like, inner electrolyte. The inner electrolyte of the reference half-cell, also referred to as the reference electrolyte, is in contact via a bridge, for example, a porous diaphragm, with the environment of the reference electrode, in order, in the measurement operation, in the case of immersion of the potentiometric sensor into a process medium to be monitored, to assure electrolytic contact between the reference electrolyte and the process medium. In this way, however, in the case of longer storage of a sensor in a single-use container, there is the danger that the reference electrolyte will dry out, or at least that air gets in via the bridge into the reference half cell space, such that the contact of the reference electrolyte with the environment is broken. Drying out can lead to drift and/or to decline of accuracy of measurement of the sensor. In the case of significant drying out of the reference electrolyte, the reference half-cell permanently stops working.